The Journal of Neuroscience, September 12, 2007, 27(37):9916-9927; doi:10.1523/JNEUROSCI.0927-07.2007
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Neurobiology of Disease
Swimming against the Tide: Mobility of the Microtubule-Associated Protein Tau in Neurons
Sven Konzack,
Edda Thies,
Alexander Marx,
Eva-Maria Mandelkow, and
Eckhard Mandelkow
Max-Planck-Unit for Structural Molecular Biology, 22607 Hamburg, Germany
Correspondence should be addressed to Eckhard Mandelkow, Max-Planck-Unit for Structural Molecular Biology, Notkestrasse 85, 22607 Hamburg, Germany. Email: mand{at}mpasmb.desy.de
Long-haul transport along microtubules is crucial for neuronal polarity, and transport defects cause neurodegeneration. Tau protein stabilizes microtubule tracks, but in Alzheimer's disease it aggregates and becomes missorted into the somatodendritic compartment. Tau can inhibit axonal transport by obstructing motors on microtubules, yet tau itself can still move into axons. We therefore investigated tau movement by live-cell fluorescence microscopy, FRAP (fluorescence recovery after photobleaching), and FSM (fluorescence speckle microscopy). Tau is highly dynamic, with diffusion coefficients of
3 µm2/s and microtubule dwell times of
4 s. This facilitates the entry of tau into axons over distances of millimeters and periods of days. For longer distances and times, two mechanisms of tau transport are observed. At low near-physiological levels, tau is cotransported with microtubule fragments from cell bodies into axons, moving at instantaneous velocities
1 µm/s. At high concentrations, tau forms local accumulations moving bidirectionally at
0.3 µm/s. These clusters first appear at distal endings of axons and may indicate an early stage of neurite degeneration.
Key words: Alzheimer's disease; axonal transport; microtubules; tau; mitochondria; synapse
Received March 1, 2007;
revised July 23, 2007;
accepted July 25, 2007.
Correspondence should be addressed to Eckhard Mandelkow, Max-Planck-Unit for Structural Molecular Biology, Notkestrasse 85, 22607 Hamburg, Germany. Email: mand{at}mpasmb.desy.de
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